Immune checkpoint blockade has formally demonstrated the clinical benefit of immunotherapy against melanoma. New immunotherapeutic modalities are currently explored to improve the management of relapsing/refractory patients. Potent antitumor vaccines would have the advantage to promote long-lasting tumor control while limiting autoimmunity. Alphavirus vectors and nonreplicating particles offer versatile platforms to deliver antigen expression and immunize against cancer. They have shown promising preclinical results and initial proof of clinical activity in melanoma. The growing number of clinically available immunomodulatory agents provides a tremendous opportunity to exploit and revisit anticancer vaccines in the setting of powerful immunotherapeutic combinations. Accelerating the evaluation of alphavirus-based vaccines in patients with immune sensitive, but still very deadly malignancies, such as melanoma, is thus extremely important.